Analysis of Gene Regulatory Networks in the Mammalian Circadian Rhythm

In today's PLoS Computation Biology:

Circadian rhythm is universally present from unicellular organisms to complex organisms and plays an important role in physiological processes such as the sleep-wake cycle in mammals. The mammalian circadian rhythm presents an excellent system for studying gene regulatory networks as a large number of genes are undergoing circadian oscillation in their expression levels. By integrating all available microarray experiments on circadian rhythm in different tissues and species in mammals, we identified a set of common circadian genes lying in the center of the circadian clock. Significant differences in the circadian oscillation of gene expression among mouse, rat, macaque, and human have been observed that underlie their physiological and behavioral differences. We constructed a gene regulatory network for the mouse circadian rhythm using knockout or mutant microarray data that have previously received little attention. Further analysis revealed not only additional feedback loops in the network contributing to the robustness of the circadian clock but also how environmental factors such as light, food, and heat can entrain the circadian rhythm. Our study provides the first gene regulatory network of the mammalian circadian rhythm at the system level. It is also the first attempt to compare gene regulatory networks of circadian rhythm in different mammalian species.